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Longitudinally Tracked, Rapid and Robust Antigen-Specific Germinal Center Responses in Non-Human Primates after a Single Nanoparticle Vaccine Immunization

38 Pages Posted: 17 May 2019 Sneak Peek Status: Published

See all articles by Colin Havenar-Daughton

Colin Havenar-Daughton

La Jolla Institute for Immunology - Division of Vaccine Discovery; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

Diane G. Carnathan

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; Emory University - Yerkes National Primate Research Center; Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Archana V. Boopathy

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

Amit A. Upadhyay

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Ben Murrell

University of California, San Diego (UCSD) - Department of Medicine

Samantha M. Reiss

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

Chiamaka A. Enemuo

Emory University - Yerkes National Primate Research Center; Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Etse H. Gebru

Emory University - Yerkes National Primate Research Center; Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Yury Chloe

Emory University - Yerkes National Primate Research Center; Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Pallavi Dhadvai

Emory University - Yerkes National Primate Research Center; Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Federico Viviano

Emory University - Yerkes National Primate Research Center; Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Kirti Kaushik

La Jolla Institute for Immunology - Division of Vaccine Discovery; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

Bryan Briney

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - Department of Immunology and Microbial Science; The Scripps Research Institute - IAVI Neutralizing Antibody Center

Dennis Burton

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - Department of Immunology and Microbial Science; The Scripps Research Institute - IAVI Neutralizing Antibody Center; Harvard University - Ragon Institute of MGH, MIT and Harvard

Steven E. Bosinger

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

William R. Schief

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - Department of Immunology and Microbial Science; The Scripps Research Institute - IAVI Neutralizing Antibody Center; Harvard University - Ragon Institute of MGH, MIT and Harvard

Darrell J. Irvine

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research; Harvard University - Ragon Institute of MGH, MIT and Harvard

Guido Silvestri

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; Emory University - Yerkes National Primate Research Center; Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Shane Crotty

La Jolla Institute for Immunology - Division of Vaccine Discovery; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; University of California, San Diego (UCSD) - Department of Medicine

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Abstract

The first immunization in a protein prime-boost vaccination is likely to be a critical event for how the immune response unfolds. However, priming immunizations generally produce little circulating antibody (Ab) or T cell responses in blood and therefore have been poorly studied in large animal models and humans. Using fine needle aspirates (FNA) of draining lymph nodes (LN), we closely tracked the primary immune response in rhesus monkeys immunized intramuscularly (IM) or subcutaneously (SubQ) with eOD-GT8 60mer nanoparticle, an epitope-directed HIV Env CD4 binding site immunogen entering human clinical trial. Significant numbers of germinal center (GC) B cells and antigen-specific CD4 T cells were detectable in the draining LN as early as 7 days post-immunization and peaked at approximately day 21. Strikingly, SubQ immunization resulted in 10-fold larger antigen-specific BGC cell responses compared to IM immunization. Antibody responses were only modestly higher after SubQ immunization. Lymphatic drainage studies revealed that SubQ immunization at the deltoid results in faster, larger, and more consistent LN drainage than IM immunization, which paralleled results from drainage studies of upper leg LNs that indicated more efficient LN drainage after SubQ administration. Together, these data indicate that, in a large animal model, robust antigen-specific GC responses can occur rapidly to a single immunization with a nanoparticle immunogen and differential injection site drainage of a vaccine substantially impacts immune responses in local LNs.

Keywords: Germinal center, antigen-specific, B cell, HIV, germline targeting, fine needle aspirate, Tfh

Suggested Citation

Havenar-Daughton, Colin and Carnathan, Diane G. and Boopathy, Archana V. and Upadhyay, Amit A. and Murrell, Ben and Reiss, Samantha M. and Enemuo, Chiamaka A. and Gebru, Etse H. and Chloe, Yury and Dhadvai, Pallavi and Viviano, Federico and Kaushik, Kirti and Briney, Bryan and Burton, Dennis and Bosinger, Steven E. and Schief, William R. and Irvine, Darrell J. and Silvestri, Guido and Crotty, Shane, Longitudinally Tracked, Rapid and Robust Antigen-Specific Germinal Center Responses in Non-Human Primates after a Single Nanoparticle Vaccine Immunization (March 14, 2019). CELL-REPORTS-D-19-01516. Available at SSRN: https://ssrn.com/abstract=3387660 or http://dx.doi.org/10.2139/ssrn.3387660
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Colin Havenar-Daughton

La Jolla Institute for Immunology - Division of Vaccine Discovery

La Jolla, CA
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

La Jolla, CA
United States

Diane G. Carnathan

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

La Jolla, CA
United States

Emory University - Yerkes National Primate Research Center

United States

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Atlanta, GA
United States

Archana V. Boopathy

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

77 Massachusetts Avenue
50 Memorial Drive
Cambridge, MA 02139-4307
United States

Amit A. Upadhyay

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Atlanta, GA
United States

Ben Murrell

University of California, San Diego (UCSD) - Department of Medicine

9500 Gilman Drive
La Jolla, CA 92093
United States

Samantha M. Reiss

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

La Jolla, CA
United States

Chiamaka A. Enemuo

Emory University - Yerkes National Primate Research Center

United States

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Atlanta, GA
United States

Etse H. Gebru

Emory University - Yerkes National Primate Research Center

United States

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Atlanta, GA
United States

Yury Chloe

Emory University - Yerkes National Primate Research Center

United States

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Atlanta, GA
United States

Pallavi Dhadvai

Emory University - Yerkes National Primate Research Center

United States

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Atlanta, GA
United States

Federico Viviano

Emory University - Yerkes National Primate Research Center

United States

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Atlanta, GA
United States

Kirti Kaushik

La Jolla Institute for Immunology - Division of Vaccine Discovery

La Jolla, CA
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

La Jolla, CA
United States

Bryan Briney

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

La Jolla, CA
United States

The Scripps Research Institute - Department of Immunology and Microbial Science

La Jolla, CA 92037
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center

La Jolla, CA
United States

Dennis Burton

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

La Jolla, CA
United States

The Scripps Research Institute - Department of Immunology and Microbial Science

La Jolla, CA 92037
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center

La Jolla, CA
United States

Harvard University - Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Steven E. Bosinger

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Atlanta, GA
United States

William R. Schief

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

La Jolla, CA
United States

The Scripps Research Institute - Department of Immunology and Microbial Science

La Jolla, CA 92037
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center

La Jolla, CA
United States

Harvard University - Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Darrell J. Irvine

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

La Jolla, CA
United States

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

77 Massachusetts Avenue
50 Memorial Drive
Cambridge, MA 02139-4307
United States

Harvard University - Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Guido Silvestri

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

La Jolla, CA
United States

Emory University - Yerkes National Primate Research Center

United States

Emory University, Yerkes National Primate Research Center, Emory Vaccine Center

Atlanta, GA
United States

Shane Crotty (Contact Author)

La Jolla Institute for Immunology - Division of Vaccine Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

University of California, San Diego (UCSD) - Department of Medicine ( email )

9500 Gilman Drive
La Jolla, CA 92093
United States

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